Optimisation of the glycerol-to-ornithine molar ratio in the feed medium for the continuous production of clavulanic acid by Streptomyces clavuligerus

被引:16
作者
Domingues, Leticia C. G. [1 ]
Teodoro, Juliana C. [2 ]
Hokka, Carlos O. [2 ]
Badino, Alberto C. [2 ]
Araujo, Maria Lucia G. C. [1 ]
机构
[1] Sao Paulo State Univ, UNESP, Inst Chem, Dept Biochem & Technol Chem, BR-14800900 Araraquara, SP, Brazil
[2] Univ Fed Sao Carlos, Dept Chem Engn, BR-13565905 Sao Carlos, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Clavulanic acid; Submerged culture; Streptomyces clavuligerus; Continuous culture; Glycerol; Ornithine; Bioprocess design; Optimisation; MANIPULATION; BIOSYNTHESIS; PHYSIOLOGY;
D O I
10.1016/j.bej.2009.05.006
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Amino acids are well metabolized by Streptomyces clavuligerus during the production of clavulanic acid using glycerol as main carbon and energy source. However, only a few amino acids such as arginine and ornithine are favorable for CA biosynthesis. The aim of this work was to optimize the glycerol:ornithine molar ratio in the feed medium containing only these compounds to maximize CA production in continuous cultivation. A minimum number of experiments were performed by means of a simple two-level full-factorial central composite design to investigate the combined effect of glycerol and ornithine feeding on the CA concentration during the intermittent and continuous process in shake-flasks. Statistical analysis of the experimental data using the response surface methodology showed that a glycerol-to-ornithine molar ratio of approximately 40:1 in the feed medium resulted in the highest CA concentration when fermentation was stopped. Under these optimized conditions, in bench-scale fermentor runs, the CA concentration reached more than double the concentration obtained in shake-flasks runs. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:7 / 11
页数:5
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